Through Transcranial Magnetic Stimulation Research Articles

Modulation of lower limb muscle corticospinal excitability during various types of motor imagery

Motor imagery (MI) is used for rehabilitation and sports training. Previous studies focusing on the upper limb have investigated the effects of MI on corticospinal excitability in the muscles involved in the imagined movement (i.e., the agonist muscles). The present study focused on several lower-limb movements and investigated the influences of MI on corticospinal excitability in the lower limb muscles. Twelve healthy individuals (ten male and two female individuals) participated in this study. Motor-evoked potentials (MEP) from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles were elicited through transcranial magnetic stimulation (TMS) to the primary motor cortex during MI of knee extension, knee flexion, ankle dorsiflexion, and ankle plantarflexion and at rest. The results showed that the RF MEPs were significantly increased during MI in knee extension, ankle dorsiflexion, and ankle plantarflexion but not in knee flexion, compared with those at rest. The TA MEPs were significantly increased during MI in knee extension and foot dorsiflexion, while MEPs were not significantly different during MI in knee flexion and foot dorsiflexion than those at rest. For the BF and SOL muscles, there was no significant MEP modulation in either MI. These results demonstrated that corticospinal excitability of the RF and TA muscles was facilitated during MI of movements in which they are active and during MI of lower-limb movements in which they are not involved. On the contrary, corticospinal excitability of the BF and SOL muscles was not facilitated by MI of lower-limb movements. These results suggest that facilitation of corticospinal excitability depends on the muscle and the type of lower-limb MI.

Identifiability Analysis and Noninvasive Online Estimation of the First-Order Neural Activation Dynamics in the Brain With Closed-Loop Transcranial Magnetic Stimulation.

Neurons demonstrate very distinct nonlinear activation dynamics, influenced by the neuron type, morphology, ion channel expression, and various other factors. The measurement of the activation dynamics can identify the neural target of stimulation and detect deviations, e.g., for diagnosis. This paper describes a tool for closed-loop sequential parameter estimation (SPE) of the activation dynamics through transcranial magnetic stimulation (TMS). The proposed SPE method operates in real time, selects ideal stimulus parameters, detects and processes the response, and concurrently estimates the input-output (IO) curve and the first-order approximation of the activated neural target. To develop a method for concurrent SPE of the first-order activation dynamics and IO curve with closed-loop TMS. First, identifiability of an integrated model of the first-order neural activation dynamics and IO curve is assessed, demonstrating that at least two IO curves need to be acquired with different pulse widths. Then, a two-stage SPE method is proposed. It estimates the IO curve by using Fisher information matrix (FIM) optimization in the first stage and subsequently estimates the membrane time constant as well as the coupling gain in the second stage. The procedure continues in a sequential manner until a stopping rule is satisfied. The results of 73 simulation cases confirm the satisfactory estimation of the membrane time constant and coupling gain with average absolute relative errors (AREs) of 6.2% and 5.3%, respectively, with an average of 344 pulses (172 pulses for each IO curve or pulse width). The method estimates the IO curves' lower and upper plateaus, mid-point, and slope with average AREs of 0.2%, 0.7%, 0.9%, and 14.5%, respectively. The conventional time constant estimation method based on the strength-duration (S-D) curve leads to 33.3% ARE, which is 27.0% larger than 6.2% ARE obtained through the proposed real-time FIM-based SPE method in this paper. SPE of the activation dynamics requires acquiring at least two IO curves with different pulse widths, which needs a controllable TMS (cTMS) device with adjustable pulse duration. The proposed SPE method enhances the cTMS functionality, which can contribute novel insights in research and clinical studies.

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

IntroductionThere is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. ObjectiveThe aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. MethodsAn 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. ResultstbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. ConclusionThe findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

Citicoline Treatment in Acute Ischemic Stroke: A Randomized, Single-Blind TMS Study.

BackgroundRecent research on animal models of ischemic stroke supports the idea that pharmacological treatment potentially enhancing intrinsic brain plasticity could modulate acute brain damage, with improved functional recovery. One of these new drugs is citicoline, which could provide neurovascular protection and repair effects.ObjectivesThe objective of this randomized, single-blind experimental study was to evaluate whether the treatment with Rischiaril® Forte was able to restore intracortical excitability measures, evaluated through transcranial magnetic stimulation (TMS) protocols, in patients with acute ischemic stroke.MethodsPatients with acute ischemic stroke were recruited and assigned to an eight-week therapy of standard treatment (control group - CG) or CDP-choline (Rischiaril® Forte, containing 1,000 mg of citicoline sodium salt) added to conventional treatment (treatment group - TG). Each subject underwent a clinical evaluation and neurophysiological assessment using TMS, pretretament and posttreatment.ResultsA total of thirty participants (mean [SD] age, 68.1 [9.6] years; 11 women [37%]) completed the study. We did not observe significant changes in clinical scores after CDP-choline treatment (all p > 0.05), but we observed a significant improvement in short-interval intracortical inhibition (SAI) (p = 0.003) in the TG group compared to the CG group.ConclusionsThe eight-week treatment with citicoline after acute ischemic stroke may restore intracortical excitability measures, which partially depends on cholinergic transmission. This study extends current knowledge of the application of citicoline in acute ischemic stroke.

P 84 Altered sensorimotor integration of afferent inhibition in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition which frequently results in sensorimotor dysfunction of the affected limb. With respect to pathophysiology an impaired interaction in sensorimotor cortex has been hypothesized 1 . Sensorimotor interactions can be assessed through transcranial magnetic stimulation (TMS) that is preceded by an electrical stimulation of peripheral motor or sensory nerves (short/ long afferent inhibition; SAI/LAI). Previous studies revealed only minor alterations of LAI using peripheral motor stimulation in CRPS 2 . This study uses a more comprehensive assessment of SAI and LAI, induced by motor and sensory peripheral stimulation, to assess interaction of the sensorimotor system in CRPS. Methods : 13 unilateral upper limb affected patients with CRPS (9 females, 54 ± 17.8 years) and 11 controls (HCs; 8 females, 52± 18.3 years) received TMS on either hemisphere. SAI and LAI were induced by a motor (m_) or sensory (s_) median nerve stimulation preceded by TMS with 20ms (m_SAI) and 200ms (m_LAI) or 23ms (s_SAI) and 203ms (s_LAI), respectively 3 . Twenty paired and single TMS stimuli were randomly applied for each condition. Results: Pain levels were 5.1±1.5/10 at rest and 7.4±2.1/10 during movements. ANOVA revealed a significant group effect for patients vs. HCs on the affected side (F=2.2, p=0.048). Post hoc tests were corrected for multiple comparisons and showed reduced inhibition in patients after sensory stimulation (s_SAI: t=-2.51, p=0.04; s_LAI: t=-2.53 p=0.038) and motor stimulation with ISI 200ms (m_LAI: t=-2.62, p=0.032). Afferent sensorimotor inhibition was lower in patients with longer disease duration (r=-0.66, p=0.014). Discussion: We demonstrate altered sensorimotor integration of afferent inhibition in CRPS. Since afferent inhibition after sensory stimulation is thought to be mediated via interconnections especially between Brodmann area 3b of somatosensory and the motor cortex, our results complement existing literature about maladaptive cortical plasticity of these regions in CRPS 4,5 . Impairment in LAI, that is thought to involve higher-order somatosensory cortical areas and the posterior parietal cortex is in line with existing literature on chronic pain 2,4 . Future longitudinal investigation should evaluate intra- and intercortical sensorimotor integration systematically in CRPS to better understand their impact in development of sensorimotor symptoms. Literature: 1 Harris AJ. Cortical origins of pathological pain. Lancet 1999. 2 Morgante et al. Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand. Mov Disord. 2017. 3 Sailer A, et al. Brain. 2003. 4 Chen et al. Modulation of motor cortex excitability by median nerve and digit stimulation. Exp Brain Res. 1999. 5 Pfannmöller et al. Investigations on maladaptive plasticity in the sensorimotor cortex of unilateral upper limb CRPS I patients. RNN. 2019.

P 23. Individualized I-waves adapted TMS – Preliminary results

Introduction. Synaptic plasticity is considered the neurophysiological correlate of learning processes in the human brain. It can be studied through transcranial magnetic stimulation (TMS). A TMS over the primary motor cortex (M1) generates descending volleys, so called I-waves (I1-I3). Their latencies can be detected with “short interval intracortical facilitation” (SICF). These latencies seem to play a pivotal role in the induction of synaptic plasticity. A paired pulse TMS, based on the defined (1.5 ms), as well as on the individual I-waves, lead to an increase in corticospinal excitability. The aim of this study was to investigate the effects of an individualized quadri-pulse theta burst stimulation (i-qTBS) with 4 bursts, based on each of the individual I1-I3- waves latencies for the first time. Methods. We studied the individual I-wave latencies through SICF in posterior-anterior (PA) and anterior-posterior (AP) current flow direction in the human M1-HAND of 12 healthy subjects (23-34 years, f=8). We used a newly engineered stimulator (MSB, Munich) to apply paired pulses with interstimulus interval of 0,1 ms to 6 ms in steps from 0,1 ms with a biphasic pulse configuration (pulse duration: 160 µs). The bursts of the qTBS consist of 4 pulses. We applied an (i)-qTBS adapted to the individual I-waves over the same hotspot (M1-HAND). Subsequently, the motor evoked potentials (MEP) and the resting motor threshold (RMT) were recorded over the period of one hour (post1-4). Results. The statistical analysis (rmANOVA) of the i-qTBS in PA direction did not show changes of the MEP-amplitude comparing the pre- to the 4 post-readings (F(4, 44) = 1.314, p = .280). The i-qTBS in AP direction also did not show any changes in MEP-amplitudes (F(4, 40) = .462, p = .763) over the course of an hour. Discussion. An i-qTBS adapted to the individual I-wave latencies did not result in any changes of corticospinal excitability. Possible reasons for this might be the high number (>200) of pre-stimuli due to the SICF, or extinction phenomena of different I1-/I3-effects. Further studies on individualized stimulation are necessary in order to analyse the neurophysiological mechanisms of the effects. This will enable a targeted individual therapeutical application of qTBS in a clinical context.

Temporally Interfering TMS: Focal and Dynamic Stimulation Location.

In this study, we present a temporal interference (TI) concept to achieve focal and steerable stimulation in the targeted brain area through transcranial magnetic stimulation (TMS). This method works by inducing two high-frequency electric fields with a slight frequency difference via two independent coils. The intrinsic nonlinear nature of the nerve membrane, which acts as a low-pass filter, does not allow the nerve to engage at high frequencies. Instead, neurons at the intersection of two electric fields can follow the frequency difference of the two fields. For 3D MRI-derived head models, the finite element method is used to compute the electric field induced by the time-varying magnetic field along with the electric field penetration depth and the activated volume for the specific coil parameters. A deeper stimulation with an acceptable spatial spread can be obtained by controlling the intersection of the fields by finding the optimal position and orientation of the two coils. Moreover, by changing the voltage ratio of the coils, and not their mechanical orientation, the intended area can be dynamically driven. The computational results show that the TI technique is an efficient approach to resolve the electric field depth-focality trade-off, which can be a reasonable alternative to complex coil designs. The system proposed in this paper shows a great promise for a more dynamic and focused magnetic stimulation.

Transcranial Magnetic Stimulation in Adults With Amblyopia.

Through transcranial magnetic stimulation (TMS) it is possible to change cortical excitability of the visual cortex, and to influence binocular balance. The main goal of our study is to assess the effect of transcranial magnetic stimulation, specifically theta burst stimulation (TBS), in a group of amblyopic volunteers measuring several visual parameters: visual acuity, suppressive imbalance, and stereoacuity. Thirteen volunteers aged 19 to 24 years, randomly split in 2 groups, underwent 1 session of continuous TBS, stimulating the right occipital lobe. The first group with 8 volunteers was exposed to active stimulation with cTBS, and the other group with 5 volunteers was exposed to placebo stimulation. Significant improvements in visual acuity, suppressive imbalance, and stereoacuity were found in the amblyopic eye after cTBS. The average value of amblyopia in visual acuity before stimulation was 0.32 ± 0.20 logMar and after cTBS was 0.19 ± 0.17 logMar. The mean value for the control group before placebo stimulation was 0.28 ± 0.17 and after placebo stimulation was 0.28 ± 0.16. The suppressive imbalance in the group of amblyope subjects stimulated before cTBS was 0.26 ± 0.18 and after was 0.12 ± 0.12; the suppressive imbalance of the control group before the placebo stimulation was 0.34 ± 0.37 and after was 0.32 ± 0.40. Visual acuity, suppressive imbalance, and stereoacuity had significant enhancements compared with baseline after cTBS over the right occipital lobe in an ambliopic population.

Crossing Death Valley: Bringing Neurotechnology to Psychiatric Clinics in Alberta, Canada.

Depression is a major public health problem, with a lifetime and 12-month prevalence estimated at 18 and 6% of adults. Depression is costly in terms of treatment and lost productivity and is the main burden of mental illness across the globe. Existing pharmacological and psychological treatments for depression result in clinically meaningful improvements in <60% of patients. An emerging treatment approach is non-invasive brain stimulation of depression-related brain targets through transcranial magnetic stimulation (TMS). In this perspective, we detail our efforts on bringing TMS to clinical populations in Alberta by utilizing a novel organizational structure that bridges the gap between academia and the health care system. The Addictions and Mental Health Strategic Clinical Network worked with stakeholders to (1) examine the evidence, (2) develop clinical tools for patient selection and protocol application, (3) create overall implementation and evaluation plans to aid in further scale and spread, and even (4) fund the purchase and deployment of devices. Through this work, five publicly supported clinics now exist in Alberta.

Oral D-Aspartate enhances synaptic plasticity reserve in progressive multiple sclerosis

Background: Synaptic plasticity reserve correlates with clinical recovery after a relapse in relapsing–remitting forms of multiple sclerosis (MS) and is significantly compromised in patients with progressive forms of MS. These findings suggest that progression of disability in MS is linked to reduced synaptic plasticity reserve. D-Aspartate, an endogenous aminoacid approved for the use in humans as a dietary supplement, enhances synaptic plasticity in mice. Objective: To test whether D-Aspartate oral intake increases synaptic plasticity reserve in progressive MS patients. Methods: A total of 31 patients affected by a progressive form of MS received either single oral daily doses of D-Aspartate 2660 mg or placebo for 4 weeks. Synaptic plasticity reserve and trans-synaptic cortical excitability were measured through transcranial magnetic stimulation (TMS) protocols before and after D-Aspartate. Results: Both TMS-induced long-term potentiation (LTP), intracortical facilitation (ICF) and short-interval ICF increased after 2 and 4 weeks of D-Aspartate but not after placebo, suggesting an enhancement of synaptic plasticity reserve and increased trans-synaptic glutamatergic transmission. Conclusion: Daily oral D-Aspartate 2660 mg for 4 weeks enhances synaptic plasticity reserve in patients with progressive MS, opening the path to further studies assessing its clinical effects on disability progression.

Effects of eccentric versus concentric contractions of the biceps brachii on intracortical inhibition and facilitation.

Differences in the neural mechanisms underpinning eccentric (ECC) and concentric (CON) contractions exist; however, the acute effects of fatiguing muscle contractions on intracortical and corticospinal excitability are not well understood. Therefore, we compared maximal ECC and CON contractions of the right biceps brachii (BB) muscle for changes in corticospinal excitability, short- (SICI) and long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF) up to 1hour post-exercise. Fourteen right-handed adults (11M/3F; 26.8±2.9year) undertook a single session of 3 sets of 10 maximal ECC or CON contractions (180-second rest between sets) on an isokinetic dynamometer (40°/s) separated by 1week, in a randomized crossover study. Maximum voluntary isometric contraction torque (MVIC), maximal muscle compound waves (MMAX ), and motor-evoked potentials elicited through transcranial magnetic stimulation (TMS) were recorded via surface electromyography from the right BB. MVIC decreased (P<0.001) immediately after ECC and CON contractions similarly, but the decrease was sustained at 1hour post-ECC contractions only. MMAX was reduced immediately (P=0.014) and 1hour post-exercise (P=0.019) only for ECC contractions. SICI and ICF increased immediately after ECC and CON contractions (P<0.001), but LICI increased only after ECC contractions (P<0.001), and these increases remained at 1hour post-ECC contractions only. These findings suggest that ECC contractions induced a longer-lasting neuromodulatory effect on intracortical inhibition and facilitation, which could indicate a central compensatory response to peripheral fatigue.

The potential dual role of transcallosal inhibition in post-stroke motor recovery.

Up to now, the mechanism of motor impairment and recovery after stroke has been thought to be based on the interhemispheric competition model. According to this model, which assumes that suppressing the excitability of contralesional hemisphere will enhance recovery by reducing transcallosal inhibition (TCI) of the stroke hemisphere, many clinical trials used non-invasive brain stimulation to improve motor function. Despite some positive findings, meta-analysis shows an important source of variability in the results, questioning whether the interhemispheric competition model would be exhaustive enough to explain the positive results or whether other mechanisms could explain the motor effects of inhibitory stimulation in the contralesional hemisphere. The goal of this study was to review the relationship between increased TCI and motor impairment after stroke.A systematic review of clinical studies investigating TCI through transcranial magnetic stimulation (TMS) in stroke patients and the relationship of this metric with motor recovery was then performed. After a literary search in PubMed eleven articles were included. The potential role of several covariates was examined and discussed.Overall, the importance of TCI as a putative mechanism for stimulation of the contralesional hemisphere seems to depend on the baseline motor function. In other words, from evidence coming mostly from chronic patients, modulation of abnormal TCI seems to be useful for patients with good motor function and less important in patients with poor motor function. TCI seems to be negatively correlated with mirror movements of the paretic hand. It can be inferred that suppressing the activity of the contralesional hemisphere could be beneficial for patients with good residual motor function and strong TCI, but not for those with poor motor function and weak TCI. Baseline motor function and measure of TCI should be taken into account for stratification of patients in clinical trials and for the design of customized treatment.

Pain-motor integration in the primary motor cortex in Parkinson's disease

BackgroundIn Parkinson's disease (PD), the influence of chronic pain on motor features has never been investigated. We have recently designed a technique that combines nociceptive system activation by laser stimuli and primary motor cortex (M1) activation through transcranial magnetic stimulation (TMS), in a laser-paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces long-term changes in motor evoked potentials reflecting M1 long-term potentiation-like plasticity, arising from pain-motor integration. ObjectiveWe here examined the possible influence of chronic pain on motor responses to Laser-PAS in patients with PD, with and without chronic pain. MethodsWe compared motor responses to Laser-PAS in healthy subjects and in patients with PD, with and without chronic pain. ResultsUnlike controls, we found reduced responses to Laser-PAS in patients with PD, with and without pain. Patients off and on dopaminergic therapy had similar responses to Laser-PAS. When comparing responses to Laser-PAS in patients with and without pain, the two patients' subgroups had similar abnormalities. When we compared patients with pain in the body region investigated with Laser-PAS, with those with pain in other body regions, we found prominent changes in patients with homotopic pain. Finally, when comparing Laser-PAS with the original PAS protocol, which combines electric peripheral nerve stimuli and TMS, in patients without pain and those with homotopic pain, we found similar responses to both techniques in patients without pain, whereas Laser-PAS induced greater abnormalities than PAS in patients with pain. ConclusionsIn PD, chronic pain degrades response to Laser-PAS through abnormal pain-motor integration.

Measures to Predict The Individual Variability of Corticospinal Responses Following Transcranial Direct Current Stimulation.

Individual responses to transcranial direct current stimulation (tDCS) are varied and therefore potentially limit its application. There is evidence that this variability is related to the contributions of Indirect waves (I-waves) recruited in the cortex. The latency of motor-evoked potentials (MEPs) can be measured through transcranial magnetic stimulation (TMS), allowing an individual’s responsiveness to tDCS to be determined. However, this single-pulse method requires several different orientations of the TMS coil, potentially affecting its reliability. Instead, we propose a paired-pulse TMS paradigm targeting I-waves as an alternative method. This method uses one orientation that reduces inter- and intra-trial variability. It was hypothesized that the paired-pulse method would correlate more highly to tDCS responses than the single-pulse method. In a randomized, double blinded, cross-over design, 30 healthy participants completed two sessions, receiving 20 min of either anodal (2 mA) or sham tDCS. TMS was used to quantify Short interval intracortical facilitation (SICF) at Inter stimulus intervals (ISIs) of 1.5, 3.5 and 4.5 ms. Latency was determined in the posterior-anterior (PA), anterior-posterior (AP) and latero-medial (LM) coil orientations. The relationship between latency, SICF measures and the change in suprathreshold MEP amplitude size following tDCS were determined with Pearson’s correlations. TMS measures, SICI and SICF were also used to determine responses to Anodal-tDCS (a-tDCS). Neither of the latency differences nor the SICF measures correlated to the change in MEP amplitude from pre-post tDCS (all P > 0.05). Overall, there was no significant response to tDCS in this cohort. This study highlights the need for testing the effects of various tDCS protocols on the different I-waves. Further research into SICF and whether it is a viable measure of I-wave facilitation is warranted.

Effects of varenicline on motor cortical plasticity in non-smokers with schizophrenia

BackgroundNicotinic acetylcholine receptors (nAChR) have been implicated in the pathophysiology of schizophrenia, and deficits in this system may contribute to high rates of cigarette smoking in this population. nAChR stimulation may modulate neuroplasticity, or long-term potentiation (LTP), which is a key mediator of cognitive performance. Varenicline is a nAChR partial agonist that may improve cognitive deficits in both smokers and non-smokers with schizophrenia; however, the mechanism by which varenicline alters cognition in schizophrenia remains unclear. Thus, the aim of this randomized, double-blind, placebo-controlled, crossover study was to determine the effects of varenicline on LTP-like plasticity indexed through transcranial magnetic stimulation (TMS) in non-smokers with schizophrenia. MethodsVarenicline (0.5mg BID × 5 doses) or placebo was administered to 9 non-smokers with schizophrenia and 10 non-smoker healthy subjects. LTP-like plasticity was induced by TMS and paired associative stimulation (PAS) at 0.1Hz to the left motor cortex and measured every 15min for two hours post-PAS. ResultsThere was a significant diagnosis × medication interaction on peak potentiation (F (3, 34)=6.04, p<0.02) and post-hoc analyses indicated that varenicline significantly increased LTP in schizophrenia and decreased LTP in healthy subjects. ConclusionsThese preliminary findings suggest that varenicline may produce differential effects in non-smoking schizophrenia compared to control subjects. Given the role of LTP in learning and memory, these observations may suggest the potential for varenicline in the treatment of cognitive deficits in patients with schizophrenia.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients’ characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies.

Functional Assessment of Corticospinal System Excitability in Karate Athletes.

ObjectivesTo investigate the involvement of the primary motor cortex (M1) in the coordination performance of karate athletes through transcranial magnetic stimulation (TMS).MethodsThirteen right-handed male karate athletes (25.0±5.0 years) and 13 matched non-athlete controls (26.7±6.2 years) were enrolled. A single-pulse TMS was applied using a figure-eight coil stimulator. Resting motor threshold (rMT) was determined. Surface electromyography was recorded from the first dorsal interosseous muscle. Motor evoked potential (MEP) latencies and amplitudes at rMT, 110%, and 120% of rMT were considered. Functional assessment of the coordination performance was assessed by in-phase (IP) and anti-phase (AP) homolateral hand and foot coordination tasks performed at 80, 120, and 180 bpm.ResultsCompared to controls, athletes showed lower rMT (p<0.01), shorter MEP latency (p<0.01) and higher MEP amplitude (p<0.01), with a significant correlation (r = 0.50, p<0.01) between rMT and MEP latency. Coordination decreased with increasing velocity, and better IP performances emerged compared to AP ones (p<0.001). In general, a high correlation between rMT and coordination tasks was found for both IP and AP conditions.ConclusionWith respect to controls, karate athletes present a higher corticospinal excitability indicating the presence of an activity-dependent alteration in the balance and interactions between inhibitory and facilitatory circuits determining the final output from the M1. Furthermore, the high correlation between corticospinal excitability and coordination performance could support sport-specific neurophysiological arrangements.

ID 70 – Cortical inhibition and excitation by bilateral transcranial alternating current stimulation

Purpose Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex. Methods We chose two amplitude ranges of the stimulations, around 25 μ A/cm2 and 63 μ A/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). Results Cortical excitability changes depended upon current density (p=.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation). Conclusions tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density.

Meta-analytic evidence for the non-modularity of pitch processing in congenital amusia

A major theme driving research in congenital amusia is related to the modularity of this musical disorder, with two possible sources of the amusic pitch perception deficit. The first possibility is that the amusic deficit is due to a broad disorder of acoustic pitch processing that has the effect of disrupting downstream musical pitch processing, and the second is that amusia is specific to a musical pitch processing module. To interrogate these hypotheses, we performed a meta-analysis on two types of effect sizes contained within 42 studies in the amusia literature: the performance gap between amusics and controls on tasks of pitch discrimination, broadly defined, and the correlation between specifically acoustic pitch perception and musical pitch perception. To augment the correlation database, we also calculated this correlation using data from 106 participants tested by our own research group. We found strong evidence for the acoustic account of amusia. The magnitude of the performance gap was moderated by the size of pitch change, but not by whether the stimuli were composed of tones or speech. Furthermore, there was a significant correlation between an individual's acoustic and musical pitch perception. However, individual cases show a double dissociation between acoustic and musical processing, which suggests that although most amusic cases are probably explainable by an acoustic deficit, there is heterogeneity within the disorder. Finally, we found that tonal language fluency does not influence the performance gap between amusics and controls, and that there was no evidence that amusics fare worse with pitch direction tasks than pitch discrimination tasks. These results constitute a quantitative review of the current literature of congenital amusia, and suggest several new directions for research, including the experimental induction of amusic behaviour through transcranial magnetic stimulation (TMS) and the systematic exploration of the developmental trajectory of this disorder.

Cortical Excitability and Agressive Behavior in Post-Traumatic Stress Disorder.

Hyperarousal and alertness play an important role in the clinical presentation of Post-traumatic stress disorder (PTSD). Strenuous effort has been made to shed light on the mechanisms that cause these symptoms of patients. Based on the claim that there is a relationship between some subtypes of hyperarousal symptoms and aggression in patients with PTSD, we aimed to examine the relationship between electrophysiological measurements that was measured through transcranial magnetic stimulation (TMS) and aggression scale scores of PTSD patients in this study. The study included 37 patients with a diagnosis of PTSD according to DSM-IV criteria and 25 healthy volunteers. Electrophysiological measurements of participants were made with TMS. The Buss Perry Aggression Questionnaires was administered to patients and control group. In the patient group, a positive correlation was found between scores of aggression and arousal symptoms. Motor excitability threshold, one of TMS measurements, which is a sign of cortical excitability, was significantly lower in the patient group than the control group. There was a negative correlation between aggression scale scores and the parameters of motor excitability threshold and cortical silent period which both shows cortical excitability of the patients. We concluded that there was an increase in cortical excitability in PTSD patients and we suggest that this increase might be associated with hyperarousal symptoms and aggressive behavior.